LIGHT (TNFSF14) promotes the differentiation of human bone marrow-derived mesenchymal stem cells into functional hepatocyte-like cells.

Liver transplantation is the most effective treatment option for patients with acute or chronic liver failure. However, the applicability and effectiveness of this modality are often limited by a shortage of donors, surgical complications, high medical costs, and the need for continuing immunosuppressive therapy. An alternative approach is liver cell transplantation.

The soluble VCAM-1 level is a potential biomarker predicting severe acute graft versus host disease after allogeneic hematopoietic cell transplantation.

Background: Severe graft versus host disease (GVHD) is the main reason for non-relapse mortality following allogeneic hematopoietic cell transplantation (HCT). We investigated the serum protein profiles of patients who had undergone HCT to identify predictive biomarkers of severe acute GVHD (aGVHD).

Methods: Serum samples were collected for 30 patients from day - 7 to day + 14 of HCT.

Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling.

Multiple myeloma (MM) is a hematological cancer causing from accumulated abnormal plasma cells. STAT3 overexpression in MM appears to be mediated by a variety of factors, and it may be associated with an adverse prognosis and play a role in microenvironment-dependent treatment resistance. Unfortunately, MM remains an incurable disease, as relapse is very common.

The c-Abl inhibitor, radotinib induces apoptosis in multiple myeloma cells via mitochondrial-dependent pathway.

Multiple myeloma (MM) is a hematological cancer resulting from accumulated abnormal plasma cells. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM.

Welfare Genome Project: A Participatory Korean Personal Genome Project With Free Health Check-Up and Genetic Report Followed by Counseling.

The Welfare Genome Project (WGP) provided 1,000 healthy Korean volunteers with detailed genetic and health reports to test the social perception of integrating personal genetic and healthcare data at a large-scale. WGP was launched in 2016 in the Ulsan Metropolitan City as the first large-scale genome project with public participation in Korea. The project produced a set of genetic materials, genotype information, clinical data, and lifestyle survey answers from participants aged 20-96.

LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells.

Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adverse effects.

Radotinib enhances cytarabine (Ara-C)-induced acute myeloid leukemia cell death.

Background: Acute myeloid leukemia (AML) is a heterogeneous disease that frequently relapses after standard chemotherapy. Therefore, there is a need for the development of novel chemotherapeutic agents that could treat AML effectively. Radotinib, an oral BCR-ABL tyrosine kinase inhibitor, was developed as a drug for the treatment of chronic myeloid leukemia.

CD45CD34CD38CD133 cells have the potential as leukemic stem cells in acute myeloid leukemia.

Background: Leukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. Studies regarding the detection of LSCs and the development of novel therapies for targeting them are extensive. The identification of LSCs and targeting therapies for them has been continuously under investigation.

Radotinib inhibits mitosis entry in acute myeloid leukemia cells via suppression of Aurora kinase A expression.

Aurora kinases play critical roles in regulating several processes pivotal for mitosis. Radotinib, which is approved in South Korea as a second-line treatment for chronic myeloid leukemia, inhibits the tyrosine kinase BCR-ABL and platelet-derived growth factor receptor. However, the effects of radotinib on Aurora kinase expression in acute myeloid leukemia are not well studied.

Rhein augments ATRA-induced differentiation of acute promyelocytic leukemia cells.

Background: Rhein (4, 5-dihydroxyanthraquinone-2-carboxylic acid), a natural anthraquinone derivative, is a traditional Chinese herb that has been used as a medication in many Asian countries. It has been used as a laxative and stomach drug for a long time in both China and Korea. It is well-known to have many pharmacological activities, such as anti-cancer, anti-bacterial, anti-fungal, anti-oxidant, anti-atherogenic, anti-angiogenic, anti-fibrosis, anti-inflammatory, hepatoprotective, and nephroprotective properties.

Targeting c-KIT (CD117) by dasatinib and radotinib promotes acute myeloid leukemia cell death.

Dasatinib and radotinib are oral BCR-ABL tyrosine kinase inhibitors that were developed as drugs for the treatment of chronic myeloid leukemia. We report here that the c-KIT (CD117) targeting with dasatinib and radotinib promotes acute myeloid leukemia (AML) cell death, and c-KIT endocytosis is essential for triggering c-KIT-positive AML cell death by dasatinib and radotinib during the early stages. In addition, dasatinib and radotinib reduce heat shock protein 90β (HSP90β) expression and release Apaf-1 in c-KIT-positive AML cells.

Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells.

Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients.

LIGHT (TNFSF14) Increases the Survival and Proliferation of Human Bone Marrow-Derived Mesenchymal Stem Cells.

LIGHT (HVEM-L, TNFSF14, or CD258), an entity homologous to lymphotoxins, with inducible nature and the ability to compete with herpes simplex virus glycoprotein D for herpes virus entry mediator (HVEM)/tumor necrosis factor (TNF)-related 2, is a member of the TNF superfamily. It is expressed as a homotrimer on activated T cells and dendritic cells (DCs), and has three receptors: HVEM, LT-β receptor (LTβR), and decoy receptor 3 (DcR3). So far, three receptors with distinct cellular expression patterns are known to interact with LIGHT.

Radotinib inhibits acute myeloid leukemia cell proliferation via induction of mitochondrial-dependent apoptosis and CDK inhibitors.

Radotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the second-line treatment of chronic myeloid leukemia. However, effects of radotinib on acute myeloid leukemia (AML) are unclear. In the present study, we observed that radotinib exerted cytotoxic effects on AML cells.

Radotinib Induces Apoptosis of CD11b+ Cells Differentiated from Acute Myeloid Leukemia Cells.

Radotinib, developed as a BCR/ABL tyrosine kinase inhibitor (TKI), is approved for the second-line treatment of chronic myeloid leukemia (CML) in South Korea. However, therapeutic effects of radotinib in acute myeloid leukemia (AML) are unknown. In the present study, we demonstrate that radotinib significantly decreases the viability of AML cells in a dose-dependent manner.

Rosmarinic acid potentiates ATRA-induced macrophage differentiation in acute promyelocytic leukemia NB4 cells.

Rosmarinic acid (RA, an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid) has a number of biological activities, but little is known about anti-leukemic activities of RA combined with all-trans retinoic acid (ATRA) against acute promyelocytic leukemia (APL) cells. We examined the differentiation marker, CD11b, in bone marrow cells (BMC) of an APL patient, in NB4 cells (APL cell line), and in normal BMC and peripheral blood mononuclear cells (PBMC) of healthy subjects by flow cytometric analysis. ATRA/RA induced expression of CD11b in the BMC of the APL patient and in NB4 cells, but not in normal BMC or PBMC.

Dasatinib accelerates valproic acid-induced acute myeloid leukemia cell death by regulation of differentiation capacity.

Dasatinib is a compound developed for chronic myeloid leukemia as a multi-targeted kinase inhibitor against wild-type BCR-ABL and SRC family kinases. Valproic acid (VPA) is an anti-epileptic drug that also acts as a class I histone deacetylase inhibitor. The aim of this research was to determine the anti-leukemic effects of dasatinib and VPA in combination and to identify their mechanism of action in acute myeloid leukemia (AML) cells.

Arsenic trioxide induces depolymerization of microtubules in an acute promyelocytic leukemia cell line.

Background: Arsenic trioxide (As(2)O(3)) is a well-known and effective treatment that can result in clinical remission for patients diagnosed with acute promyelocytic leukemia (APL). The biologic efficacy of As(2)O(3) in APL and solid tumor cells has been explained through its actions on anti-proliferation, anti-angiogenesis, and apoptotic signaling pathways. We theorize that As(2)O(3) activates a pathway that disrupts microtubule dynamics forming abnormal, nonfunctioning mitotic spindles, thus preventing cellular division.

Emodin and rhein inhibit LIGHT-induced monocytes migration by blocking of ROS production.

LIGHT is known to act as a novel mediator for atherogenesis. Furthermore, it has been reported that emodin, an active component extracted from rhubarb, can stop the growth of cancer cells. However, it is not known if emodin exerts anti-atherogenic effects in the human monocyte, THP-1, following treatment with LIGHT.

Gefitinib enhances arsenic trioxide (AS2O3)-induced differentiation of acute promyelocytic leukemia cell line.

Gefitinib (Iressa, ZD1839), a selective epidermal growth factor receptor tyrosine kinase inhibitor, inhibits growth, invasion and colony formation of various cancer cells. However, little is known about the effect of combination of gefitinib and arsenic trioxide (ATO) on differentiation of acute promyelocytic leukemia (APL). Therefore, we investigated whether gefitinib had any role in the ATO-induced differentiation of NB4 cells (APL cell line).

Evodiamine and rutaecarpine inhibit migration by LIGHT via suppression of NADPH oxidase activation.

LIGHT acted as a new player in the atherogenesis. The dried, unripe fruit of Evodia Fructus (EF) has long been used as a traditional Chinese herbal medicine, and is currently widely used for the treatment of headache, abdominal pain, vomiting, colds and reduced blood circulation. Evodiamine and rutaecarpine are active components of EF.

A pilot dose-escalating study of alemtuzumab plus cyclosporine for patients with bone marrow failure syndrome.

The pathogenesis of bone marrow failure syndrome (BMFS) involves both T- and B-cells. Since alemtuzumab (ALM) is a monoclonal anti-CD52 antibody that targets both cell types, we assessed the effects of treatment with ALM and cyclosporine (CS) on 19 patients with BMFS (median age 48 years; range, 16-74 years), including 14 with severe/very severe aplastic anemia (AA), 3 with transfusion-dependent AA and 1 each with myelodysplastic syndrome (MDS) and pure red cell aplasia (PRCA). The dose of ALM was escalated from dose cohort I (10mg on day 1, 20mg on day 2, and 30 mg on day 3) to dose cohort II (30 mg/d for 3 days) plus CS for at least 6 months.

LPS induces inflammatory responses in human aortic vascular smooth muscle cells via Toll-like receptor 4 expression and nitric oxide production.

Inflammation is an important event in the development of vascular diseases such as hypertension, atherosclerosis, and restenosis. In addition, the stimulation of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) induces the release of critical proinflammatory cytokines that activate potent immune responses. In this study, LPS was found to induce TLR4 expression and increased nitric oxide (NO) production by increasing the expression of inducible nitric oxide synthase (iNOS).

Enhanced bactericidal function by WKYMVm in patients with acute leukemia.

We have previously shown that the novel hexapeptide WKYMVm can stimulate bactericidal activity in neutrophils obtained from neutropenic patients treated with chemotherapeutic agents for solid tumors. To extend these observations, we evaluated whether WKYMVm can enhance leukocyte bactericidal activity in patients with acute leukemia (AL). Using blood samples withdrawn from 28 AL patients and 31 healthy controls, we found that, in the absence of exogenous WKYMVm, WKYMVm receptor and bactericidal activity did not differ between patients and controls.